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Shokoufeh Savaj MD Associate Professor of Medicine Firouzgar hospital Iran University of Medical Sciences Acute Kidney Injury (Acute Renal Failure )

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Definition Rapid decline in glomerular filtration rate (GFR) over hours to days

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Diagnostic criteria for ARF Abrupt (within 48 hours) absolute increase in the serum creatinine concentration of 0.3 mg/dL from baseline A percentage increase in the serum creatinine concentration of 50 percent Oliguria of less than 0.5 mL/kg per hour for more than six hours

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Classifications for Acute Renal Failure

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Classification Prerenal (55%) Renal(40%) Post renal (5%) Prerenal (55%) Renal(40%) Post renal (5%)

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Pathogenesis of prerenal Azotemia Fall in mean systemic arterial pressure, Reduced stretch by arterial (e.g., carotid sinus) and cardiac baroreceptors Neurohormonal responses t( activation sympathetic nervous system,RAS system and vasopressin release. Vasoconstrictrion in musculocutaneous and splanchnic circulations Preserved cardiac and cerebral perfusion pressure Decrease salt loss and stimulation of thirst and salt appetite

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Local myogenic reflex (autoregulation). Angiotensin II increases biosynthesis of vasodilator prostaglandins (e.g., prostaglandin E 2 and prostacyclin Afferent arteriolar vasodilation Constriction of efferent arterioles. Increased filtration fraction Maintenance of intraglomerular pressure and GFR Severe hypoperfusion, GFR falls, leading to prerenal ARF.

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Prerenal ARF Hypovolemia A. Increased extracellular fluid losses B. Gastrointestinal fluid loss C. Renal fluid loss D. Extravascular sequestration E. Decreased intake Altered renal hemodynamics resulting in hypoperfusion A. Low cardiac output state B. Systemic vasodilation C. Renal vasoconstriction D. Impairment of renal autoregulatory responses E. Hepatorenal syndrome

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Glomerular and microcirculation Interstitial nephritis Acute tubular necrosis Diseases of larger renal vessels Intrinsic ARF

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Renovascular obstruction A. Renal artery obstruction B. Renal vein obstruction Diseases of the glomeruli or vasculature A. Glomerulonephritis or vasculitis B. thrombotic microangiopathy, malignant hypertension, collagen vascular diseases (systemic lupus erythematosus, scleroderma), disseminated intravascular coagulation, preeclampsia

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Renal Vein thrombosis

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Renal artery stenosis

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Post Streptococcal Glomerulonephritis

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Acute tubular necrosis A. Ischemia B. Infection, with or without sepsis syndrome C. Toxins: 1. Exogenous: 2. Endogenous: rhabdomyolysis, hemolysis

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Decrease blood flow and oxygen delivery Increase oxygen consumption and direct cellular toxicity Renal medullary hypoxia

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Interstitial nephritis A. Allergic B. Infection C. Infiltrations D. Inflammatory, nonvascular: Sjgren's syndrome, tubulointerstitial nephritis with uveitis Intrinsic ARF

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Intratubular obstruction A. Endogenous B. Exogenous Intrinsic ARF

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Post renal

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Ureterovesical junction Obstruction

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Laboratory studies in prerenal acute renal failure (ARF) and acute tubular necrosis (ATN) PrerenalATN Urine Sodium (meq/L) 30 Urine Osmolarity> 500 mosmol 20< 20 Fractional Excretion of Sodium < 1%> 2%

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Fractional Excretion of Sodium U Na x P Cr FE Na % = x 100 P Na x U Cr U Na x P Cr FE Na % = x 100 P Na x U Cr

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Diagnosis of ARF EtiologyEpidemiologyClinical features Serum studiesUrine studies Prerenal ARFMost common History of poor fluid intake,Worsening heart failure Treatment with ACE/ARB/NSAI D Clincal signs of volume depletion High BUN /Cr > 20 is suggestive Hyaline casts FENa < 1% Urine Na < 10 mmol/L Urine SG > 1018

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Diagnosis of ARF EtiologyEpidemiologyClinical features Serum studies Urine studies IschemiaSevere hemorrhage or hypotension Muddy browun tubular or epithelial cast casts FENa > 1% Urine Na >20 mmol/L Urine SG

EtiologyEpidemiologyClinical featuresSerum studies Urine studies Exposure to endogenus toxins RhabdomyolysisPost ictal,prolonged ischemia or immobilization Increased myoglobin and Creatine kinase U/A positive for heme With no RBC Hemolysis :recent blood transfusion Fever, transfusion reaction Pink plasma, increased LDH same as above Tumor lysis :recent chemotherapy Hyperuricemi a,increased LDH Urate crystals Multiple myelomaIndividuals >60yrs age, contitutional symptoms Anemia,mono clonal spike Proteinuria spike on urine electrophoresis Ethylene glycolHistory of alcohol abuse,altered mental state High anion gap acidosis,with osmolal gap,positive toxicity Oxalate crystals

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EtiologyEpidemiologyClinical features Serum studies Urine studies Allergic interstitial nephritis Recent medication exposure Fever,rash, arthralgia EosinophiliaWhite cell casts,eosinophiluria Acute bilateral pyelonephritis Fever, flank pain and tenderness Positive blood cultures leukocytes, proteinuria,positive urine culture Postrenal ARFHistory of renal stones or prostatic disease Palpable bladder, flank or abdominal pain Usually normal.hematuria if due to stones

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Novel biomarkers of acute kidney injury *Low molecular weight proteins: ( Alpha1-Microglobulin (alpha1-M), beta2-Microglobulin (beta2-M), retinol binding protein (RBP), adenosine deaminase binding protein (ABP), and urinary cystatin C *Tubular enzymes :Urinary tubular enzymes consist of proximal renal tubular epithelial antigen (HRTE-1), alpha-Glutathione S- transferase (alpha-GST), pi-Glutathione S-transferase (pi-GST), gamma-Glutamyltranspeptidase (gamma-GT), Alanine aminopeptidase (AAP), Lactate dehydrogenase (LDH), N-acetyl-beta- glucosaminidase (NAG), and Alkaline phosphatase (ALP).

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Kidney injury molecule 1 (KIM1) Transmembrane protein in proximal tubular cells Phagocytic properties of tubular cell DD prerenal from ATN Neutrophil gelatinase associated lipocalin (NGAL) Protein in granules with tissue Protective effect of in proximal Increases 2 hours after ischemic injury Novel biomarkers of acute kidney injury

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Classification/staging system for acute kidney injury*

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